Differential expression of two genes Oct‐4 and <scp>MUC</scp>5<scp>AC</scp> associates with poor outcome in patients with gastric cancer

Javanbakht, Milad; Akhavan-Moghadam, Jamal; Talaei, Amir Jouya; Aghyani, Maryam; Mozafari, Mohammad Reza; Khedmat, Leila; Mohebbi, Mahdi

doi:10.1111/1440-1681.12840

Cited by 18 publications

(10 citation statements)

References 37 publications

(86 reference statements)

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“…CA125 is used biomarker for detection and screening of ovarian cancer [30,31]. Other untouchable mucins, including MUC17 [32], MUC6, MUC5AC [33,34], MUC5B [35,36], MUC12 [37], and MUC4 [38][39][40], are known to be associated with cancer risk and development.…”

Section: Discussionmentioning

confidence: 99%

Untouchable genes in the human genome: Identifying ideal targets for cancer treatment

2019

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Background: Usually, genes with a higher-than-expected number of somatic mutations in tumor samples are assumed to be cancer related. We identified genes with a fewer-than-expected number of somatic mutations -"untouchable genes". Methods:To predict the expected number of somatic mutations, we used a linear regression model with the number of mutations in the gene as an outcome, and gene characteristics, including gene size, nucleotide composition, level of evolutionary conservation, expression level and others, as predictors. Analysis of residuals from the regression model was used to compare the observed and predicted number of mutations. Results:We have identified 19 genes with a less-than-expected number of loss-off-function (nonsense, frameshift or pathogenic missense) mutations-i.e., untouchable genes. The number of silent or neutral missense mutations in untouchable genes was equal or higher than the expected number. Many mucins, including MUC16, MUC17, MUC6, MUC5AC, MUC5B, and MUC12, are untouchable. We hypothesized that untouchable mucins help tumor cells to avoid immune response by providing a protective coat that prevents direct contact between effector immune cells, e.g., cytotoxic T-cells, and tumor cells. Survival analysis of available TCGA data demonstrated that overall survival of patients with low (below the median) expression of untouchable mucins was better compared to patients with high expression of untouchable mucins. Aside from mucins, we have identified a number of other untouchable genes.Conclusions: Untouchable genes may be ideal targets for cancer treatment since suppression of untouchable genes is expected to inhibit survival of tumor cells.

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Section: Discussionmentioning

confidence: 99%

Untouchable genes in the human genome: Identifying ideal targets for cancer treatment

2019

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“…Evidence suggests that MUC expression is involved in the invasion and metastasis of various malignancies, including gallbladder cancer [19], breast cancer [20], ovarian cancer [21], gastric carcinoma [22,23], pancreatic carcinoma [24][25][26], ampullary cancer [27,28], lung cancer [16,29], prostate cancer [30], renal cell carcinoma [31], and appendiceal carcinoma [32]. However, the prognostic value of MUC expression in CRC remains controversial [33][34][35][36][37].…”

Section: Introductionmentioning

confidence: 99%

Prognostic and Clinicopathological Significance of MUC Family Members in Colorectal Cancer: A Systematic Review and Meta-Analysis

Zuo

Liu

et al. 2019

Gastroenterology Research and Practice

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Objective. To assess the association between MUC expression levels in colorectal cancer (CRC) tissues and prognosis and investigate the associations between MUC expression levels and CRC clinicopathological characteristics. Methods. The PubMed, Embase, Cochrane Library, and Web of Science databases were searched from inception through September 13, 2019, to identify studies investigating the association between MUC expression levels in CRC tissues and prognosis. Pooled hazard ratios (HRs) or odds ratio (ORs) with 95% confidence intervals (CIs) were used to evaluate associations between MUC expression levels and prognosis or clinicopathological characteristics, respectively. The heterogeneity between studies was assessed by the I2 values, whereas the likelihood of publication bias was assessed by Egger’s linear regression and Begg’s rank correlation test. Results. Among 33 included studies (n=6032 patients), there were no associations between combined MUC phenotype expression levels and overall survival (OS) or disease-free survival (DFS)/relapse-free survival (RFS) in patients with CRC. In subgroup analyses, the upregulated MUC1 expression (HR=1.50; 95% CI, 1.29–1.74; P<0.00001) was associated with poor OS. However, the upregulated MUC2 expression (HR=0.64; 95% CI, 0.52–0.79; P<0.00001) was associated with better OS. Furthermore, a high level of MUC1 expression (HR=1.99; 95% CI, 0.99–3.99; P=0.05) was associated with shorter DFS/RFS. However, patients with a low level of MUC2 tumors showed better DFS/RFS than patients with a high level of MUC2 tumors (HR=0.71; 95% CI, 0.49–1.04; P=0.08; P=0.0.009, I2=67%) and MUC5AC expression (HR=0.56; 95% CI, 0.38–0.82; P=0.003) was associated with longer DFS/RFS. In addition, a high level of MUC1 expression was associated with CRC in the rectum, deeper invasion, lymph node metastasis, distant metastasis, advanced tumor stage, and lymphatic invasion. A high level of MUC2 expression had a protective effect. High secretion of MUC5AC is associated with colon cancer compared with rectal cancer. Conclusion. The protein expression of MUC1 might be a poor biomarker in colorectal cancer and might play a role in tumor transformation and metastasis. However, the protein expression of MUC2 expression might have a protective effect. Furthermore, randomized controlled trials (RCTs) of large patients are needed to confirm the results.

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“…296 studies were evaluated by browsing the full‐text. Eventually, 57 studies containing 7401 patients were enrolled in our study 10–18,27–74 . Sixteen types of cancers were included, including acute myeloid leukemia, bladder cancer, breast cancer, cervical cancer, colorectal cancer, esophageal cancer, gallbladder adenocarcinoma, gastric cancer, head and neck cancer, LIHC, lung cancer, neuroblastomas, ovarian cancer, pancreatic cancer, papillary renal cell carcinoma, and prostate cancer.…”

Section: Resultsmentioning

confidence: 99%

Diagnostic significance and carcinogenic mechanism of pan‐cancer gene POU5F1 in liver hepatocellular carcinoma

Zhang

2020

Cancer Medicine

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Background The prognostic and clinicopathological significance of POU Class 5 Homeobox 1 (POU5F1) among various cancers are disputable heretofore. The diagnostic value and functional mechanism of POU5F1 in liver hepatocellular carcinoma (LIHC) have not been studied thoroughly. Methods An integrative strategy of meta‐analysis, bioinformatics, and wet‐lab approach was used to explore the diagnostic and prognostic significance of POU5F1 in various types of tumors, especially in LIHC. Meta‐analysis was utilized to investigate the impact of POU5F1 on prognosis and clinicopathological parameters in various cancers. The expression level and diagnostic value of POU5F1 were assessed by qPCR in plasma collected from LIHC patients and controls. The correlation between POU5F1 and tumor infiltrating immune cells (TIICs) in LIHC was evaluated by CIBERSORT. Gene set enrichment analysis (GSEA) was performed based on TCGA. Hub genes and related pathways were identified on the basis of co‐expression genes of POU5F1. Results Elevated POU5F1 was associated with poor OS, DFS, RFS, and DSS in various cancers. POU5F1 was confirmed as an independent risk factor for LIHC and correlated with tumor occurrence, stage, and invasion depth. The combination of POU5F1 and AFP in plasma was with high diagnostic validity (AUC = 0.902, p < .001). Specifically, the level of POU5F1 was correlated with infiltrating levels of B cells, T cells, dendritic cells, and monocytes in LIHC. GSEA indicated that POU5F1 participated in multiple cancer‐related pathways and cell proliferation pathways. Moreover, CBX3, CCHCR1, and NFYC were filtered as the central hub genes of POU5F1. Conclusion Our study identified POU5F1 as a pan‐cancer gene that could not only be a prognostic and diagnostic biomarker in various cancers, especially in LIHC, but functionally carcinogenic in LIHC.

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Differential expression of two genes Oct‐4 and MUC5AC associates with poor outcome in patients with gastric cancer

Cited by 18 publications

References 37 publications

Untouchable genes in the human genome: Identifying ideal targets for cancer treatment

Untouchable genes in the human genome: Identifying ideal targets for cancer treatment

Prognostic and Clinicopathological Significance of MUC Family Members in Colorectal Cancer: A Systematic Review and Meta-Analysis

Diagnostic significance and carcinogenic mechanism of pan‐cancer gene POU5F1 in liver hepatocellular carcinoma

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